Mge1, a nucleotide exchange factor of Hsp70, acts as an oxidative sensor to regulate mitochondrial Hsp70 function

Marada, Adinarayana; Allu, Praveen Kumar; Murari, Anjaneyulu; PullaReddy, BhoomiReddy; Tammineni, Prasad; Thiriveedi, Venkata Ramana; Danduprolu, Jayasree; Sepuri, Naresh Babu V.

doi:10.1091/mbc.e12-10-0719

Cited by 39 publications

(57 citation statements)

References 58 publications

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“…Protein folding inside mitochondria is promoted through a successive action of the Hsp70 complex (Scc1 with co-chaperone Mdj1) and the Hsp60 complex [73]. In addition to Ssc1-Mdj1 protein folding, Ssc1 can form a complex with the co-chaperone Mge1 to regulate resistance to oxidative stress [74]. Mge1-Mge1 dimers decrease in response to oxidative stress, promoting Ssc1-Mge1 interaction, thereby up-regulating chaperone activity to refold damaged proteins [74].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to Ssc1-Mdj1 protein folding, Ssc1 can form a complex with the co-chaperone Mge1 to regulate resistance to oxidative stress [74]. Mge1-Mge1 dimers decrease in response to oxidative stress, promoting Ssc1-Mge1 interaction, thereby up-regulating chaperone activity to refold damaged proteins [74]. When yeast cells are challenged with oxidative stress, several mitochondrial proteins become oxidized including Hsp60 [72].…”

Section: Discussionmentioning

confidence: 99%

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Quantitative proteomics of the yeast Hsp70/Hsp90 interactomes during DNA damage reveal chaperone-dependent regulation of ribonucleotide reductase

Truman

Kristjansdottir

Wolfgeher

et al. 2015

Journal of Proteomics

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The highly conserved molecular chaperones Hsp90 and Hsp70 are indispensible for folding and maturation of a significant fraction of the proteome, including many proteins involved in signal transduction and stress response. To examine the dynamics of chaperone-client interactions after DNA damage, we applied quantitative affinity-purification mass spectrometry (AP-MS) proteomics to characterize interactomes of the yeast Hsp70 isoform Ssa1 and Hsp90 isoform Hsp82 before and after exposure to methyl methanesulfonate. Of 256 proteins identified and quantified via 16O/18O labeling and LC-MS/MS, 142 are novel Hsp70/90 interactors. Nearly all interactions remained unchanged or decreased after DNA damage, but 5 proteins increased interactions with Ssa1 and/or Hsp82, including the ribonucleotide reductase (RNR) subunit Rnr4. Inhibiting Hsp70 or 90 chaperone activity destabilized Rnr4 in yeast and its vertebrate homolog hRMM2 in breast cancer cells. In turn, pre-treatment of cancer cells with chaperone inhibitors sensitized cells to the RNR inhibitor gemcitabine, suggesting a novel chemotherapy strategy. All MS data have been deposited in the ProteomeXchange with identifier PXD001284.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics of the yeast Hsp70/Hsp90 interactomes during DNA damage reveal chaperone-dependent regulation of ribonucleotide reductase

Truman

Kristjansdottir

Wolfgeher

et al. 2015

Journal of Proteomics

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“…Recently, the ubiquitous nature of enzymatic reduction was highlighted with the discovery of the first mitochondrial MSR substrate, the adenine nucleotide exchange factor Mge1 that acts as an oxidative sensor during mitochondrial protein import. Upon oxidation Mge1 is reduced by MsrB (Marada et al, 2013;Allu et al, 2015).…”

Section: Reversible Protein Oxidationmentioning

confidence: 99%

Oxidised protein metabolism: recent insights

Samardzic

Rodgers

2017

Biological Chemistry

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Abstract:The 'oxygen paradox' arises from the fact that oxygen, the molecule that aerobic life depends on, threatens its very existence. An oxygen-rich environment provided life on Earth with more efficient bioenergetics and, with it, the challenge of having to deal with a host of oxygen-derived reactive species capable of damaging proteins and other crucial cellular components. In this minireview, we explore recent insights into the metabolism of proteins that have been reversibly or irreversibly damaged by oxygen-derived species. We discuss recent data on the important roles played by the proteasomal and lysosomal systems in the proteolytic degradation of oxidatively damaged proteins and the effects of oxidative damage on the function of the proteolytic pathways themselves. Mitochondria are central to oxygen utilisation in the cell, and their ability to handle oxygen-derived radicals is an important and still emerging area of research. Current knowledge of the proteolytic machinery in the mitochondria, including the ATPdependent AAA+ proteases and mitochondrial-derived vesicles, is also highlighted in the review. Significant progress is still being made in regard to understanding the mechanisms underlying the detection and degradation of oxidised proteins and how proteolytic pathways interact with each other. Finally, we highlight a few unanswered questions such as the possibility of oxidised amino acids released from oxidised proteins by proteolysis being re-utilised in protein synthesis thus establishing a vicious cycle of oxidation in cells.

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“…In fact, both HSP70 and chaperone protein 60 have been shown to bind to nascent polypeptide chains to induce protein folding; moreover, these proteins also promote the rapid degradation and removal of denatured proteins. Multiple studies indicate that most small molecule heat‐shock proteins (HSPs), as well as α‐crystallin, can be combined with ATP to protect cells from stress‐mediated damage and improve cellular tolerance to various stimuli (Marada et al , ). Treatment with potassium tetraborate increased the levels of these chaperones after 48 h but later decreased them at 72 h. HSP expression is likely to be affected by this type of stress (Medicherla & Goldberg, ); furthermore, NADPH oxidase might also be inhibited as a key enzyme in oxygen radical production by improving peroxidase levels (Asai et al , ).…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of the mango anthracnose pathogen Colletotrichum gloeosporioides treated with borate highlights distinct mitochondrial response mechanisms

Chen

et al. 2019

Plant Pathology

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Mango anthracnose caused by the fungal pathogen Colletotrichum gloeosporioides results in substantial economic losses in postharvest fruits. Borate is an effective fungicide against C. gloeosporioides. It appears to induce mitochondrial degradation and dysfunction in the fungal conidia, but the underlying molecular mechanism remains unclear. This study investigated the effects of borate on this pathogen by examining its mitochondrial proteins, which were extracted from C. gloeosporioides mycelium after borate treatment (5 or 10 mm potassium tetraborate for 48 and 72 h) and characterized using proteomic analysis (two‐dimensional electrophoresis, 2‐DE; and mass spectrometry, MS) and bioinformatics. In total, 600 protein spots were separated by 2‐DE, and 115 of these appeared to be differentially expressed proteins (DEPs). Among the DEPs, 58 were identified using MALDI‐TOF‐TOF MS/MS. Borate treatment was found to alter the expression levels of proteins involved in seven different metabolic pathways, mostly related to energy supply and/or biosynthesis. The effect of borate on mRNA expression levels of 17 genes involved in these metabolic pathways was confirmed by real‐time quantitative reverse transcription PCR (qRT‐PCR). The results suggest that borate might have distinct effects on mitochondrial function in C. gloeosporioides and could be used to control anthracnose in postharvest mango fruits.

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Mge1, a nucleotide exchange factor of Hsp70, acts as an oxidative sensor to regulate mitochondrial Hsp70 function

Abstract: Yeast Mge1, the cochaperone of mitochondrial heat shock protein 70 (mHsp70), is essential for exchanging ATP for ADP on mHsp70 and thus for recycling of mHsp70 for mitochondrial protein import and folding. Mge1 acts as an oxidative sensor to regulate mHsp70 function.

Cited by 39 publications

References 58 publications

Quantitative proteomics of the yeast Hsp70/Hsp90 interactomes during DNA damage reveal chaperone-dependent regulation of ribonucleotide reductase

Quantitative proteomics of the yeast Hsp70/Hsp90 interactomes during DNA damage reveal chaperone-dependent regulation of ribonucleotide reductase

Oxidised protein metabolism: recent insights

Proteomic analysis of the mango anthracnose pathogen Colletotrichum gloeosporioides treated with borate highlights distinct mitochondrial response mechanisms

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